Franková D, Zidek Z
Laboratory of Immunology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Eur J Immunol. 1998 Mar;28(3):838-43. doi: 10.1002/(SICI)1521-4141(199803)28:03<838::AID-IMMU838>3.0.CO;2-T.
The effect of IFN-gamma to stimulate formation of nitric oxide (NO) by normal murine peritoneal macrophages (M phi) has been found to be completely dependent on the ability of IFN-gamma to activate secretion of TNF-alpha. The NO-stimulatory effect of IFN-gamma was abolished by anti-TNF-alpha antibodies, the inhibitory intervention of which could be fully reversed by exogenously supplied TNF-alpha. Accordingly, the failure of M phi from C3H/HeJ mice to secrete TNF-alpha upon stimulation with IFN-gamma was associated with their complete incapability to generate NO, unless they were simultaneously treated with IFN-gamma + TNF-alpha. Collectively, the data document that similar to the NO up-regulatory action of other cytokines, the effect of IFN-gamma is not independent, but depends on a synergistic cooperation with the self-produced TNF-alpha. The findings thus indicate that a widespread opinion claiming that IFN-gamma per se is able to stimulate biosynthesis of NO needs revision.
已发现，γ干扰素刺激正常小鼠腹腔巨噬细胞（M phi）形成一氧化氮（NO）的效应完全依赖于γ干扰素激活肿瘤坏死因子-α（TNF-α）分泌的能力。γ干扰素的NO刺激效应被抗TNF-α抗体消除，而这种抑制作用可通过外源性提供TNF-α完全逆转。因此，C3H/HeJ小鼠的M phi在用γ干扰素刺激时未能分泌TNF-α，这与它们完全无法产生NO有关，除非同时用γ干扰素+TNF-α处理。总体而言，这些数据证明，与其他细胞因子的NO上调作用类似，γ干扰素的效应并非独立的，而是依赖于与自身产生的TNF-α的协同合作。这些发现表明，一种普遍观点认为γ干扰素本身能够刺激NO的生物合成，这一观点需要修正。
